CN103923829B - The needle of bar magnet method extraction apparatus and sleeve pipe mobile system are applied with it - Google Patents

The needle of bar magnet method extraction apparatus and sleeve pipe mobile system are applied with it Download PDF

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Publication number
CN103923829B
CN103923829B CN201310014647.5A CN201310014647A CN103923829B CN 103923829 B CN103923829 B CN 103923829B CN 201310014647 A CN201310014647 A CN 201310014647A CN 103923829 B CN103923829 B CN 103923829B
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needle
sleeve pipe
end block
support
casing support
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CN103923829A (en
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刘新志
赵海峰
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Changzhou Genmag Biotechnology Co Ltd
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Changzhou Genmag Biotechnology Co Ltd
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    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12MAPPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M47/00Means for after-treatment of the produced biomass or of the fermentation or metabolic products, e.g. storage of biomass
    • C12M47/04Cell isolation or sorting
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K1/00General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
    • C07K1/14Extraction; Separation; Purification
    • C07K1/145Extraction; Separation; Purification by extraction or solubilisation
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09Recombinant DNA-technology
    • C12N15/10Processes for the isolation, preparation or purification of DNA or RNA
    • C12N15/1003Extracting or separating nucleic acids from biological samples, e.g. pure separation or isolation methods; Conditions, buffers or apparatuses therefor
    • C12N15/1006Extracting or separating nucleic acids from biological samples, e.g. pure separation or isolation methods; Conditions, buffers or apparatuses therefor by means of a solid support carrier, e.g. particles, polymers
    • C12N15/1013Extracting or separating nucleic acids from biological samples, e.g. pure separation or isolation methods; Conditions, buffers or apparatuses therefor by means of a solid support carrier, e.g. particles, polymers by using magnetic beads

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  • Proteomics, Peptides & Aminoacids (AREA)
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Abstract

The invention provides a kind of needle and sleeve pipe mobile system of the biologically active substance extraction apparatus for bar magnet method, it comprises: needle and needle travel mechanism, sleeve pipe and cannula translating mechanism and vibrating mechanism, described vibrating mechanism can produce vibration and make cannula translating mechanism carry out up-down vibration, wherein, needle can vertically insert and depart from sleeve pipe, and sleeve pipe vertically can insert and depart from sample preparation district, vibrating mechanism comprises lever arm, movable fulcrum and rotating mechanism.Present invention also offers the application of described system in biologically active substance extraction apparatus.Present invention also offers the biologically active substance extraction apparatus using described system.Present invention also offers the method using described instrument Isolation and purification nucleic acid.

Description

The needle of bar magnet method extraction apparatus and sleeve pipe mobile system are applied with it
Technical field
The present invention relates to biology and apparatus field.Concrete, the invention provides a kind of needle and sleeve pipe mobile system of the biologically active substance extraction apparatus for bar magnet method, and in biologically active substance extraction apparatus, use the method for described system.
Background technology
Extract cell at multiple fields such as modern molecular biology research, clinical disease diagnosis, blood transfusion, food safety detection, and the biologically active substance such as protein, nucleic acid has vital role.Wherein, the biologically active substance compound that nucleic acid is become by many nucleotide polymerization is one of the most base substance of life.Nucleic acid is extensively present in all animals, vegetable cell, microorganism, in organism.Different according to chemical constitution, nucleic acid can be divided into Yeast Nucleic Acid, is called for short RNA and thymus nucleic acid, is called for short DNA.DNA is the essential substance basis storing, copy and convey hereditary information, and RNA plays an important role in protein building-up process.The development of biotechnology is maked rapid progress, along with round pcr is in the application of every field, comprise medical science aspect disease detection, agriculture aspect detection GMOs and other very many-sided application etc., need high-throughout sample biologically active substance to extract and the method for full-automatic biologically active substance extraction and instrument.
Paramagnetic particle method that developed recently gets up utilize can the magnetic bead of specific recognition cell, protein or nucleic acid to extract biologically active substance.Magnetic bead can be combined specifically with nucleic acid molecule, then under the influence of a magnetic field, separates from the active macromolecules blood, animal tissues, food, pathogenic micro-organism equal samples.
Paramagnetic particle method automatic extracting instrument is divided into again bar magnet method and suction method.Suction method is undertaken by automatic pipetting device.For paramagnetic particle method instrument for extracting nucleic acid, add lysate, magnetic bead absorption by automatic pipetting device; Take solution away, add rinsing liquid, magnetic bead adsorbs, and takes rinsing liquid away, adds elution buffer.Owing to not taking magnetic bead away time suction method exists and removes waste liquid, pipettor can not lean on magnetic bead too near, in case magnetic bead together with waste liquid by the problem taken out, affect elution efficiency and purity.
It is the technology that developed recently gets up that bar magnet method is extracted, and its principle is that magnetic separating device is immersed liquid, makes the particle that can be attracted magnetically in mixture concentrate on separating device surface by the action of a magnetic field.Wherein in a kind of mode, magnetic separating device is a sleeve pipe, makes sleeve pipe produce magnetic by inserting bar magnet, attract the granular absorption that can be attracted magnetically in mixture to sleeve surface, when bar magnet is detached, sleeve pipe loses magnetism, and the particle be attracted magnetically departs from sleeve pipe.The flux of bar magnet method instrument for extracting nucleic acid has 8,16,32,96 passages usually.Drive the mechanism of bar magnet that bar magnet can be driven to move up and down in sleeve pipe, contribute to the cracking of leaching process and rinsing and purifying.
Summary of the invention
The invention provides a kind of needle and sleeve pipe mobile system of the biologically active substance extraction apparatus for bar magnet method, additionally provide the biologically active substance extraction apparatus using described system.System of the present invention and extraction apparatus can be applicable to the multiple fields such as clinical disease diagnosis, transfusion safety, Forensic Identification, environmental microorganism detection, food safety detection, molecular biology research, for Isolation and purification biologically active substance, such as cell, albumen and nucleic acid.
Concrete, the invention provides a kind of needle for biologically active substance extraction apparatus and sleeve pipe mobile system, it is characterized in that, described needle and sleeve pipe mobile system comprise:
Needle 7 and needle travel mechanism 48, needle travel mechanism comprises needle support 8 and needle lifting mechanism 33, and needle is removably fixed on needle support, wherein, by moving up and down of needle lifting mechanism, makes needle vertically to insert and to depart from sleeve pipe,
Sleeve pipe 4 and cannula translating mechanism 16, cannula translating mechanism comprises casing support 6 and telescopic lifter structure 18, sleeve pipe is removably fixed on casing support, wherein, by moving up and down of telescopic lifter structure, make sleeve pipe can vertically insert and depart from sample preparation district below it, and cannula translating mechanism 16 can up-down vibration
With
For supporting the mechanism rack 13 of described needle travel mechanism 48 and cannula translating mechanism 16.
In one aspect of the invention, go back involving vibrations mechanism 19 in the system of the invention described above, described vibrating mechanism can produce and export vibration, makes cannula translating mechanism 16 carry out up-down vibration.
In one aspect of the invention, the needle support 8 in the system of the invention described above comprises needle support end block 9 and needle supported arm 34, and needle is removably fixed on needle supported arm; Described needle lifting mechanism comprises the needle be arranged on below needle support end block and promotes end block 17, when needle promotion end block moves upward, promote needle support end block and move upward, thus promotion needle support moves upward.
Of the present invention in another, in said system, needle promotes end block 17 with needle support 8 is separable, when needle support contacts with casing support in the process declined, needle promotes end block and is separated with needle support, and needle support is supported by casing support and together moves with casing support.
In one aspect of the invention, in the system of the invention described above, casing support 6 comprises casing support end block 35 and casing support arm 5, and sleeve pipe is removably fixed on casing support arm; Described telescopic lifter structure comprises the sleeve pipe lifting end block 36 be arranged on below casing support end block, when sleeve pipe lifting end block moves upward, pushing set tube support end block moves upward, thus pushing set tube support moves upward, lifting end block is when moving downward, and casing support end block is elevated end block according to action of gravity and sleeve pipe and synchronously moves downward.
Of the present invention in another, the lifting end block of sleeve pipe described in said system and casing support are separable.
In one aspect of the invention, arrange cover tube vibration push rod 26 below the casing support end block of said system, it is connected with vibrating mechanism 19, conduction vibration.
In one aspect of the invention, go back involving vibrations mechanism 19 in described system, described vibrating mechanism can produce and export vibration, makes cannula translating mechanism 16 carry out up-down vibration.Of the present invention in another, described vibrating mechanism comprises lever arm, movable fulcrum and rotating mechanism, wherein said rotating mechanism has wheel disc and axle center, when described rotating mechanism rotates around axle center, the outer rim of its wheel disc can promote lever arm and rotate around movable fulcrum, thus produces vibration.An aspect wherein, the feature of system of the present invention is, described lever arm, movable fulcrum and rotating mechanism be arranged so that anyway the amplitude size of the vibration produced changes, its lower-most point exporting the amplitude of the vibration of cannula translating mechanism is constant.Thus, how the amplitude of the vibration no matter vibrating mechanism produces and exports changes, and also namely no matter how its conduction changes to the amplitude of casing support, adopts the lower-most point of the amplitude of the pipe box of the instrument of the extraction biologically active substance of present system constant.
In the present invention, the some profile outer rim of described rotating mechanism (particularly eccentric rotary mechanism) being formed into the shortest distance in its axle center is called nearest profile point.In the present invention, the working order of vibrating mechanism refers to that the rotating mechanism of vibrating mechanism rotates around axle center, and the outer rim of its wheel disc promotes state when lever arm rotates around balance pivot.In the present invention, when the nearest profile point of rotating mechanism described in vibrating mechanism produces pushing effect (being generally nearest profile point and the lever arm contacts of rotating mechanism) to lever arm, in vibrating mechanism, lever arm rotates around balance pivot, and lever arm now can be supplied to be called lowest amplitude position of the fulcrum around the position of rotating lever fulcrum.In one embodiment of the present invention, in system of the present invention, the lever arm of vibrating mechanism, being set to of movable fulcrum and rotating mechanism, in working order, the change of the position of movable fulcrum is limited to lowest amplitude position of the fulcrum.Thus, how the displacement that the rotating mechanism of no matter vibrating mechanism can be made to promote lever arm changes, also no matter how the position of movable fulcrum on lever arm adjusts, also how the amplitude of the i.e. vibration no matter vibrating mechanism produces and exports changes, the lower-most point of the amplitude of its vibration exported is all constant, thus how the amplitude making no matter vibrating mechanism export to casing support changes, the lower-most point of its amplitude is constant, also namely makes to adopt the lower-most point of the amplitude of the pipe box of the biologically active substance of present system extraction instrument constant.In the system of the present invention, vibrating mechanism is by a fixing some output amplitude on lever arm, and this point is normally relatively rotating the opposite side of fulcrum of mechanism and lever arm contacts point.How the amplitude no matter vibrating mechanism exports to casing support changes, constant in the lower-most point of the amplitude of this point of fixity, also namely makes to adopt the biologically active substance of present system to extract the lower-most point of the amplitude of the pipe box of instrument constant.
In one aspect of the invention, the vibrating mechanism of said system comprises straight line lever arm 22, mobile fulcrum and eccentric wheel 21, and mobile fulcrum can move along lever arm, its travel direction is the axial direction due of lever arm, and wherein eccentric minimum radius is equal to the distance of lever arm with its axle center.
In one aspect of the invention, the mobile fulcrum of said system comprises traversing carriage 23, traversing carriage driving mechanism 24 and mobile fulcrum shaft 37, lever arm has the hollow groove parallel with its upper surface, mobile fulcrum shaft is through hollow groove, move in hollow groove under traversing carriage driving mechanism drives, form the mobile fulcrum of lever.
In one aspect of the invention, in the system of the invention described above, casing support has at least one casing support arm, and preferably, casing support has two casing support arms, and supported arm has can the bushing slot of fixed sleeving.
In one aspect of the invention, in the system of the invention described above, needle support has at least one needle supported arm, and preferably, needle support has two supported arms, supported arm has the needle groove can fixing needle.
In one aspect of the invention, described in the system of the invention described above, needle is permanent magnet material.
In one aspect of the invention, described in the system of the invention described above, sleeve pipe is nonmagnetic substance.
In one aspect of the invention, the system of the invention described above is used for biologically active substance extraction apparatus, and wherein biologically active substance can be cell, protein or nucleic acid.
In one aspect of the invention, the system of the invention described above is used for the instrument of Isolation and purification nucleic acid.
Present invention also offers the method using above-mentioned needle and sleeve pipe mobile system to drive needle and sleeve pipe movement in bar magnet method biologically active substance extraction apparatus.
Present invention also offers a kind of instrument for extracting biologically active substance, comprising:
Shell and base plate 1,
Worktable 15, it has sample preparation district,
Needle of the present invention as above and sleeve pipe mobile system, wherein said system comprises:
Needle 7 and needle travel mechanism 48, needle travel mechanism comprises needle support 8 and needle lifting mechanism 33, and needle is removably fixed on needle support, wherein, by moving up and down of needle lifting mechanism, makes needle vertically to insert and to depart from sleeve pipe,
Sleeve pipe 4 and cannula translating mechanism 16, cannula translating mechanism comprises casing support 6 and telescopic lifter structure 18, sleeve pipe is removably fixed on casing support, wherein, by moving up and down of telescopic lifter structure, make sleeve pipe vertically can insert and depart from sample preparation district, in addition, cannula translating mechanism 16 can up-down vibration;
For supporting the mechanism rack 13 of described needle travel mechanism 48 and cannula translating mechanism 16,
With
Vibrating mechanism 19, described vibrating mechanism can produce and export vibration, makes cannula translating mechanism 16 carry out up-down vibration.Wherein, vibrating mechanism comprises lever arm, movable fulcrum and rotating mechanism, wherein said rotating mechanism has wheel disc and axle center, when described rotating mechanism rotates around axle center, the outer rim of its wheel disc can promote lever arm and rotate around movable fulcrum, thus produces vibration.
Lever arm described in instrument of the present invention, movable fulcrum and rotating mechanism be arranged so that anyway the amplitude size of the vibration produced changes, the lower-most point of its amplitude produced is constant.Thus, how the amplitude of the vibration no matter vibrating mechanism produces and exports changes, and also namely no matter how its conduction changes to the amplitude of casing support, and the lower-most point of the amplitude of the pipe box of instrument of the present invention is constant.
Rotating mechanism in the vibrating mechanism of instrument of the present invention has wheel disc and the axle center of ad hoc type line profile, and when these rotatable parts rotate around axle center, the outer rim of its wheel disc can promote lever arm and rotate around movable fulcrum, produces and exports vibration.Of the present invention in one of them, described rotating mechanism is eccentric rotary mechanism, and the Bu center, axle center of its rotatable parts, is eccentric rotary mechanism.Eccentric rotary mechanism can be eccentric wheel etc.
In the present invention, the some profile outer rim of described rotating mechanism (particularly eccentric rotary mechanism) being formed into the shortest distance in its axle center is called nearest profile point.In the present invention, the working order of vibrating mechanism refers to that the rotating mechanism of vibrating mechanism rotates around its axle center, and the outer rim of its wheel disc promotes state when lever arm rotates around balance pivot.In the present invention, when the nearest profile point of rotating mechanism described in vibrating mechanism produces pushing effect (being generally nearest profile point and the lever arm contacts of rotating mechanism) to lever arm, in vibrating mechanism, the position of the balance pivot that lever arm rotates about it is called lowest amplitude position of the fulcrum.In one embodiment of the present invention, in instrument of the present invention, the lever arm of vibrating mechanism, being set to of movable fulcrum and rotating mechanism, in working order, the change of the position of movable fulcrum is limited to lowest amplitude position of the fulcrum.Thus, how the displacement that the rotating mechanism of no matter vibrating mechanism can be made to promote lever arm changes, also no matter how the position of movable fulcrum on lever arm adjusts, also how the amplitude of the i.e. vibration no matter vibrating mechanism produces and exports changes, the lower-most point of amplitude described in it is all constant, thus how the amplitude making no matter vibrating mechanism export to casing support changes, the lower-most point of its amplitude is constant, also namely makes the lower-most point of the amplitude of the pipe box of instrument of the present invention constant.Usually, vibrating mechanism is by a fixing some output amplitude on lever arm, and this point is normally relatively rotating the opposite side of fulcrum of mechanism and lever arm contacts point.How the amplitude no matter vibrating mechanism exports to casing support changes, constant in the lower-most point of the amplitude of this point of fixity, also namely makes the lower-most point of the amplitude of the pipe box of instrument of the present invention constant.
The rotating mechanism used in the present invention can be eccentric rotary mechanism, and it has the wheel disc of axle center (i.e. turning point) and ad hoc type line profile, Bu center, its axle center.Preferably, described rotating mechanism can adopt circular as profile, is eccentric wheel.Adopt circular wheel to have easily manufactured, technique is simple, and the amplitude exporting vibration is easy to the advantages such as adjustment.In addition, the cam with non-central axle center also can as eccentric rotary mechanism of the present invention.
Have central hub but also can be used for the present invention by vibrative rotating mechanism, such as outline is oval cam.
In the present invention, movable fulcrum and the way of contact of lever arm can be that fulcrum contacts or embed the groove or hollow groove etc. that are arranged on lever arm with the lower edge of lever arm.
In another embodiment of the present invention, movable fulcrum is set to along the mobile fulcrum of the lower edge of lever arm or the groove be arranged on lever arm or hollow groove movement, can to produce the vibration of the amplitude with continuous variable thus.Such as, movable fulcrum is mounted in the fulcrum shaft on Mobile base, and fulcrum shaft contacts with the lower edge of lever arm, or the groove inserted on lever arm or hollow groove, under the driving of Mobile base, move formation fulcrum along lever arm.
Lever arm is preferably set to linear lever arm.Described lever arm can have the groove parallel with its upper surface or hollow groove, may be used for for a point cantact.Mobile fulcrum can move along the edge of lever arm (lower edge) or the groove be located on lever arm or hollow groove, and its travel direction is the axial direction due of lever arm.In this case, to be set to the axle center of eccentric rotary mechanism equal to the distance of lever arm with described axle center to the minor increment of profile outer rim for vibrating mechanism.When eccentric rotary mechanism is eccentric wheel, it is equal to the distance of lever arm with its axle center that vibrating mechanism is set to eccentric minimum radius (namely axle center is to the minor increment of wheel rim).In this case, the radial direction of eccentric wheel minimum radius is vertical with the travel direction (i.e. the axis of lever arm) that lever moves fulcrum.
Of the present invention wherein in another, mobile fulcrum comprises traversing carriage 23, traversing carriage driving mechanism 24 and mobile fulcrum shaft 37, lever arm has the hollow groove parallel with its upper surface, mobile fulcrum shaft is through hollow groove, move in hollow groove under traversing carriage driving mechanism drives, form the mobile fulcrum of lever.
In one aspect of the invention, lever arm has vibrating wheels 25, and described vibrating wheels contacts with telescopic lifter structure, conduction vibration, and described vibrating wheels and rotating mechanism lay respectively at the both sides of mobile fulcrum.
Present invention also offers a kind of method using above-mentioned instrument Isolation and purification biologically active substance.
May be used in the system of the invention described above extracting biologically active substance, such as cell, protein or nucleic acid.
It can be the instrument for Isolation and purification nucleic acid in the instrument of the invention described above.
Accompanying drawing explanation
By reading the detailed description done non-limiting example done with reference to the following drawings, other features, objects and advantages of the present invention will become more obvious:
Fig. 1 is first direction stereographic map in accordance with a preferred embodiment of the present invention;
Fig. 2 is second direction stereographic map in accordance with a preferred embodiment of the present invention;
Fig. 3 is side cross sectional views in accordance with a preferred embodiment of the present invention;
Fig. 4 is side cross sectional views in accordance with a preferred embodiment of the present invention;
Fig. 5 is sectional block diagram in accordance with a preferred embodiment of the present invention.
Reference numeral
1 base plate
2 heated sample grooves
3 non-heated workspace
4 sleeve pipes
5 casing support arms
6 casing supports
7 needles
8 needle supports
9 needle support end blocks
10 optical axises
11 motors one
12 motors two
13 mechanism racks
14 mechanism's platforms
15 traversers
16 cannula translating mechanism
17 needles promote end block
18 telescopic lifter structures
19 vibrating mechanisms
20 eccentric wheel drive-motor
21 eccentric wheels
22 lever arms
23 traversing carriages
24 traversing carriage driving mechanisms
25 vibrating wheels
26 cover tube vibration push rods
31 screw mandrels one
32 screw mandrels two
33 needle lifting mechanisms
34 needle supported arms
35 casing support end blocks
36 sleeve pipe lifting end blocks
37 move fulcrum shaft
48 needle travel mechanisms
Embodiment
For a better understanding and interpretation of the present invention, the present invention is described in further detail below with reference to accompanying drawings.
Fig. 1 is the first direction stereographic map adopting the needle of a preferred embodiment of the present invention and the instrument for extracting biologically active substance of sleeve pipe mobile system.Described instrument can be used for Isolation and purification nucleic acid.This instrument has shell (not illustrating at accompanying drawing) and base plate 1, needle 7 and needle travel mechanism 48, sleeve pipe 4 and cannula translating mechanism 16, for supporting the support 13 of described needle travel mechanism and cannula translating mechanism, and for generation of vibration, make cannula translating mechanism carry out the vibrating mechanism 19 of up-down vibration.
Shell (not illustrating at accompanying drawing) can by instrument internal and air spaced apart, in order to avoid sample contamination and damage parts.Housing face-plate is generally metallic substance and makes.Shell can have the sample window that can open and close, for putting into and taking out sample.Shell can have the viewing window made with transparent material.Sample window and viewing window can be same parts.Shell can have the external apparatus interface be connected with peripheral equipment in addition, the display screen of operation display interface, various manipulation of switches, button or button etc.
Sleeve pipe is the pipe with closed bottom and hollow tube chamber.Sleeve pipe can have such as elongated cylinder form.The material of sleeve pipe is normally nonmagnetic.The Choice and design of its material and thickness is for not weakened field or only affect magnetic field a little, but needs the magnetic field that ensures to produce the biological sample that can attract magnetic bead or band magnetic bead outward at sleeve pipe when inserting needle.
Needle can vertically insert and depart from sleeve pipe.The bottom (namely inserting one end of sleeve pipe) of needle has magnetic.When needle insert with contact or close to sleeve bottom time, magnetic field can be produced outward at sleeve pipe, thus realize sleeve pipe to the magnetic bead in the outer solution of sleeve pipe or the absorption of biological sample and the disengaging of being with magnetic bead.In the present embodiment, the bottom of needle has permanent magnet, and band is magnetic thus.In other embodiments of the present invention, needle produces magnetic (electromagnet) by electromagnetic action.
Fig. 2 is the above-mentioned second direction stereographic map of the instrument for extracting biologically active substance according to adopting the preferred embodiments of the present invention needle and sleeve pipe mobile system.
As depicted in figs. 1 and 2, the described instrument for extracting biologically active substance has the worktable 15 that can move horizontally.As shown in Figure 2, the worktable 15 that can move horizontally has sample preparation district.Sample preparation district can comprise workspace, sample cell, sample well, or its combination.Sample preparation district can the sample cell of processing sample or sample well for arranging, or for placing the vessel of load sample, as type culture plates such as single or single centrifuge tube, 24 orifice plates or 96 orifice plates, also can put the non-standard culture plate of needs.
In illustrated instrument, worktable has Liang Zu sample preparation district with corresponding two groups of needles and cannula system.Mei Zu sample preparation district comprises the non-heated workspace 3 in two groups of heated sample grooves 2 and these two groups of sample cells respectively.Heated sample groove can insert single or single centrifuge tube.Non-heated workspace can put single or single centrifuge tube, also can put the type culture plate such as 24 orifice plates or 96 orifice plates, can also put the non-standard culture plate of needs.Worktable 15 is by the driving mechanisms control be arranged at below it, can move in the horizontal direction, make sample preparation district move to the below of sleeve pipe, sleeve pipe vertically can insert and depart from the sample cell in sample preparation district, or be fixed on test tube or the EP pipe of sample cell, or the hole of culture plate.
The described instrument for extracting biologically active substance has needle 7 and needle travel mechanism 48.Needle travel mechanism 48 comprises needle support 8 and needle lifting mechanism 33.
Needle support 8 comprises needle support end block 9 and needle supported arm 34.Needle is removably fixed on needle supported arm.Diagram the preferred embodiments of the present invention for extracting in the instrument of biologically active substance, needle support has two needle supported arms be arranged in parallel.Needle support also can only have a needle supported arm, also can be above two.The quantity of the fixable needle of each needle supported arm can adjust as required, and often group is 1-12 root needle usually, and common is 4,6 or 12 needles.In another embodiment, needle supported arm can fix needle group, and each needle group has arranges needle more, 24 needles (spread pattern is 4 × 6) of such as corresponding culture plate, 96 needles (spread pattern is 8 × 12) etc.In the present embodiment, the bottom of needle has permanent magnet, and band is magnetic thus.In other embodiments of the present invention, needle also produces magnetic by electromagnetic action.
Needle lifting mechanism comprises needle and promotes end block 17, motor 12, leading screw 2 32 and nut transmission pair, and motor drives promotion end block 17 to move upward by leading screw and nut transmission pair.Needle promotes end block 17 and is arranged on below needle support end block 9.Needle promotes end block and can contact with needle support end block.When motor by leading screw and nut transmission pair drive promote end block move upward time, needle promotes end block and contacts with needle support end block, and promotes needle support end block and move upward, thus promotion needle support moves upward.
The described instrument for extracting biologically active substance also has sleeve pipe 4 and cannula translating mechanism 16.Cannula translating mechanism comprises casing support 6 and telescopic lifter structure 18.Casing support comprises casing support end block 35 and casing support arm 5.Diagram the preferred embodiments of the present invention for extracting in the instrument of biologically active substance, casing support has two casing support arms be arranged in parallel.Casing support also can only have a casing support arm, also can be above two.Sleeve pipe is removably fixed on casing support arm.The quantity of the fixable sleeve pipe of each casing support arm can adjust as required.The quantity of sleeve pipe can adjust as required, and often group is 1-12 root sleeve pipe usually.Common is 4,6 or 12 sleeve pipes.In another embodiment, casing support arm can fixed sleeving group, and each sleeve pipe group has many bar casing tubes, 24 sleeve pipes (spread pattern is 4 × 6) of such as corresponding culture plate, 96 sleeve pipes (spread pattern is 8 × 12) etc.
Telescopic lifter structure comprises sleeve pipe lifting end block 36, motor 11, leading screw 1 and nut transmission pair.Motor drives sleeve pipe lifting end block to move up or down by leading screw and nut transmission pair.Sleeve pipe lifting end block is arranged on below casing support end block.Sleeve pipe lifting end block can with the contact of casing support end block.When motor drives sleeve pipe lifting end block to move upward by leading screw and nut transmission pair, sleeve pipe lifting end block can contact with casing support end block, and pushing set tube support end block moves upward, thus pushing set tube support moves upward.When motor drives sleeve pipe lifting end block to move downward by leading screw and nut transmission pair, casing support end block is elevated end block according to action of gravity and sleeve pipe and synchronously moves downward, thus drive casing support moves downward.
Fig. 3 and Fig. 4 is the side cross sectional views of described employing needle of the present invention and sleeve pipe mobile system.As can be seen from Fig. 3 and Fig. 4, sleeve pipe lifting end block 36 is separable with casing support end block 35, and namely sleeve pipe lifting end block and casing support are separable, realize the vibration of sleeve pipe thus and move up and down and can be manipulated by different institutions independently.
Sleeve pipe lifting end block is arranged at below casing support end block 35.When motor drives sleeve pipe lifting end block to move upward by leading screw and nut transmission pair, pushing set tube support moves upward.When motor drives sleeve pipe lifting end block to move downward by leading screw and nut transmission pair, casing support end block is elevated end block according to action of gravity and sleeve pipe and synchronously moves downward, thus drive casing support moves downward.
Use system of the present invention for extracting in the instrument of biologically active substance, as shown in Figure 2 and Figure 5, arrange cover tube vibration push rod 26 below casing support end block, it is connected with vibrating mechanism, conduction vibration.
In illustrated instrument, sleeve pipe lifting end block is also arranged on below casing support end block, and the length of its upper surface is identical with the lower surface of casing support end block with width, can be elevated end block play support and pushing effect to sleeve pipe.The upper surface length of cover tube vibration push rod is less than the lower surface of casing support end block with width, is arranged on below casing support end block.In the middle of sleeve pipe lifting end block, there is cavity.Cover tube vibration push rod is also arranged on below casing support end block, and its upper surface length is less than the lower surface of casing support end block with width.In the middle of sleeve pipe lifting end block, have cavity, cover tube vibration push rod can be allowed to pass, and the upper end of cover tube vibration push rod contacts with casing support end block, and lower end contacts with the vibrating mechanism be arranged on below cannula translating mechanism.
In one aspect of the invention, needle promotes end block 17 with needle support end block 9 is separable.Needle promotes a side contacts of end block and needle support end block.When motor drives promotion end block to move upward by leading screw and nut transmission pair, promote needle support by needle support end block and move upward.Needle can be made so upwards to depart from from sleeve pipe.Moving downward of needle support is according to action of gravity.The needle of instrument of the present invention promotes end block and needle support is separable, and this design can realize the abundant close contact of needle termination and sleeve bottom, simplifies the requirement to automatically controlled part, and the phenomenon preventing needle from impacting sleeve bottom occurs.
Fig. 3 illustrates the working order of described instrument when needle inserts sleeve pipe.Needle 4 inserts sleeve pipe, and its bottom contacts with the bottom of sleeve pipe.Now needle promotion end block 17 is separated with needle support end block 9, and needle support 8 is supported by casing support 6 and together moves with casing support.
Another kind of embodiment is that needle 4 inserts sleeve pipe, arrives the position of the predetermined bottom closest to sleeve pipe, and now needle promotion end block 17 is separated with needle support end block 9, and needle support is supported by casing support and together moves with casing support.The position that predetermined needle bottom arrives closest to sleeve bottom can be limited by casing support 6 and arranging of needle support 8, such as be set to needle supported arm and casing support arm contact, or needle supported arm contacts with the male member that casing support arm is arranged, described male member can be cushioning material preparation.
Fig. 4 illustrates the working order that sleeve pipe is separated with needle.Needle promotes a side contacts of end block 17 and needle support end block 9.When motor drives needle promotion end block to move upward by leading screw and nut transmission pair, promote needle support by needle support end block and move upward, needle is separated with sleeve pipe.
In addition, sleeve pipe lifting end block 35 contacts with casing support end block 36, and when motor drives sleeve pipe lifting end block to move upward by leading screw and nut transmission pair, pushing set tube support moves upward.When motor drives sleeve pipe lifting end block to move downward by leading screw and nut transmission pair, casing support moves downward with sleeve pipe lifting end block under gravity.
Pass through when needing sleeve pipe to vibrate thus the biological sample of the magnetic bead that adsorbs outward of wash-out sleeve pipe or band magnetic bead time, needle support end block promotes needle support and moves upward, and sleeve pipe is separated with needle.Sleeve pipe lifting end block and casing support end block disengage.Casing support vibrates under vibrating mechanism effect.
Insert when needing sleeve pipe or the hole of the centrifuge tube of sample area or culture plate time, sleeve pipe lifting end block 35 contacts with casing support end block 36, when motor drives sleeve pipe lifting end block to move upward by leading screw and nut transmission pair, pushing set tube support moves upward and leaves sample area.When motor drives sleeve pipe lifting end block to move downward by leading screw and nut transmission pair, casing support moves downward with sleeve pipe lifting end block under gravity, inserts sample area.
In addition, as shown in the figure, described needle travel mechanism and cannula translating mechanism are arranged on mechanism's platform 14, are supported by mechanism rack 13.
The both sides of needle support end block 9, sleeve pipe lifting end block 36 and casing support end block 35 have perforation, article two, be vertically arranged on the perforation of the optical axis 10 on mechanism's platform through described needle support end block 9, sleeve pipe lifting end block 36 and casing support end block 35, restriction and fixed action are risen to needle support end block, sleeve pipe lifting end block and casing support end block.
The both sides that needle promotes end block also have perforation, are passed by another two optical axises.
Instrument for extracting biologically active substance of the present invention has vibrating mechanism, and described vibrating mechanism can produce vibration, makes cannula translating mechanism drive sleeve pipe to carry out up-down vibration.The sleeve pipe of the instrument of extraction biologically active substance of the present invention can carry out up-down vibration up to the frequency of 20Hz.Described vibrating mechanism of the present invention comprises lever arm, mobile fulcrum and eccentric stiffener, and described mobile fulcrum can move along lever arm.Instrument for extracting biologically active substance of the present invention in the course of the work, the upper and lower fast vibration of one of them procedure calls needle sheath.According to different job requirements, this vibration will have different amplitudes and frequency.The amplitude being arranged to vibrate and the frequency of the vibrating mechanism of the instrument for extracting biologically active substance of the present invention are adjustable; and anyway amplitude adjusts; the starting point (lower-most point) of its amplitude is unanimously identical; thus reach the object of the mechanisms such as protection sheath; together with further feature of the present invention; instrument of the present invention is made to have low noise, the advantage of high life.
As shown in Figure 5, driving mechanism of the present invention comprises linear lever arm 22, traversing carriage 23, mobile fulcrum shaft 37, drive the driving mechanism 24 that traversing carriage moves horizontally, contact and the vibrating wheels 25 of conduction vibration with the cover tube vibration push rod 26 of telescopic lifter structure, and eccentric wheel 21 and eccentric wheel drive-motor 20.Lever arm is linear pattern, has the hollow groove parallel with lower edge with its upper limb.Mobile fulcrum shaft, through hollow groove, can move in hollow groove along lever arm direction under traversing carriage driving mechanism drives, and forms the mobile fulcrum of lever.To contact with the cover tube vibration push rod 26 of telescopic lifter structure and the vibrating wheels 25 of conduction vibration and eccentric wheel lay respectively at the both sides of mobile fulcrum.Eccentric wheel and lever arm contacts, when eccentric wheel rotates, cause and be subjected to displacement at the lever arm (power arm) of the eccentric wheel side of fulcrum, the lever arm (resistance arm) of the opposite side of fulcrum and vibrating wheels then synchronously carry out rightabout displacement, and namely the rotation around fulcrum occurs lever arm.Eccentric rotation makes vibrating wheels vibrate, thus makes cannula translating mechanism drive sleeve pipe to carry out up-down vibration.Also namely, in the vibrating mechanism of the instrument for extracting biologically active substance of the present invention, producing vibration by eccentric stiffener (being eccentric wheel in embodiment), the speed of controlled frequency, together with the movement of the position of mobile fulcrum on lever arm, controlling the size of amplitude.
In the instrument of the preferred embodiments of the present invention shown in Fig. 5, eccentric wheel directly contacts with linear lever arm, eccentric minimum radius (namely axle center is to the minor increment of wheel rim) is equal to the distance of lever arm with its axle center, namely to move the travel direction (i.e. lever arm) of fulcrum vertical for radial direction and the lever of eccentric wheel minimum radius, now, no matter how fulcrum moves in the hollow groove of lever arm, when the contact of eccentric wheel and lever arm generation minimum radius, vibrating wheels is all in the lower-most point of its amplitude.No matter how eccentric rotating speed changes, no matter also how the position of mobile fulcrum on lever arm changes, namely regardless of amplitude and the frequency of vibrating wheels, the lower-most point of vibrating wheels is all constant, and namely the lower-most point of vibration occurs sleeve pipe is constant.
In other embodiments of the present invention, also eccentric wheel can be replaced to realize object of the present invention with cam.
The instrument of extraction biologically active substance of the present invention is by adopting above-mentioned vibrating mechanism, vibrational frequency and amplitude can be adjusted arbitrarily, no matter how amplitude adjusts simultaneously, the minimum start position of various amplitude is all identical, the setting range of vibrational frequency can be increased substantially, whole instrument is made to have low noise, the advantage of high life.
Although describe in detail about example embodiment of the present invention and advantage thereof, being to be understood that when not departing from the protection domain of spirit of the present invention and claims restriction, various change, substitutions and modifications can being carried out to these embodiments.For other examples, those of ordinary skill in the art should easy understand maintenance scope in while, the order of processing step can change.
In addition, range of application of the present invention is not limited to the technique of the specific embodiment described in specification sheets, mechanism, manufacture, material composition, means, method and step.From disclosure of the present invention, to easily understand as those of ordinary skill in the art, for the technique existed at present or be about to develop, mechanism, manufacture, material composition, means, method or step later, wherein their perform the identical function of the corresponding embodiment cardinal principle that describes with the present invention or obtain the identical result of cardinal principle, can apply according to the present invention to them.Therefore, claims of the present invention are intended to these technique, mechanism, manufacture, material composition, means, method or step to be included in its protection domain.

Claims (17)

1. for needle and the sleeve pipe mobile system of biologically active substance extraction apparatus, it is characterized in that, described needle and sleeve pipe mobile system comprise:
Needle (7) and needle travel mechanism (48), needle travel mechanism comprises needle support (8) and needle lifting mechanism (33), needle is removably fixed on needle support, wherein, by moving up and down of needle lifting mechanism, needle is made vertically to insert and to depart from sleeve pipe
Sleeve pipe (4) and cannula translating mechanism (16), cannula translating mechanism comprises casing support (6) and telescopic lifter structure (18), sleeve pipe is removably fixed on casing support, wherein, by moving up and down of telescopic lifter structure, make sleeve pipe can vertically insert and depart from sample preparation district below it, and cannula translating mechanism (16) can up-down vibration
With
For supporting the mechanism rack (13) of described needle travel mechanism (48) and cannula translating mechanism (16).
2. system according to claim 1, go back involving vibrations mechanism (19) in described system, described vibrating mechanism can produce and export vibration, makes cannula translating mechanism (16) carry out up-down vibration.
3. the system described in claim 1 or 2, wherein needle support (8) comprises needle support end block (9) and needle supported arm (34), and needle is removably fixed on needle supported arm; Described needle lifting mechanism comprises the needle be arranged on below needle support end block and promotes end block (17), when needle promotion end block moves upward, promote needle support end block and move upward, thus promotion needle support moves upward.
4. system according to claim 3, wherein needle promotes end block (17) with needle support (8) is separable, when needle support contacts with casing support in the process declined, needle promotes end block and is separated with needle support, and needle support is supported by casing support and together moves with casing support.
5. the system described in claim 1 or 2, wherein casing support (6) comprises casing support end block (35) and casing support arm (5), and sleeve pipe is removably fixed on casing support arm; Described telescopic lifter structure comprises sleeve pipe lifting end block (36) be arranged on below casing support end block, when sleeve pipe lifting end block moves upward, pushing set tube support end block moves upward, thus pushing set tube support moves upward, sleeve pipe lifting end block is when moving downward, and casing support end block is elevated end block according to action of gravity and sleeve pipe and synchronously moves downward.
6. system according to claim 5, wherein said sleeve pipe lifting end block and casing support are separable.
7. system according to claim 6, wherein arrange cover tube vibration push rod (26) below casing support end block, it is connected with vibrating mechanism (19), conduction vibration.
8. the system described in claim 1 or 2, wherein casing support has at least one casing support arm, supported arm has the bushing slot of fixed sleeving, and wherein needle support has at least one needle supported arm, supported arm has the needle groove of fixing needle.
9. system according to claim 8, wherein casing support has two casing support arms, and needle support has two supported arms.
10. system according to claim 2, wherein said vibrating mechanism comprises straight line lever arm (22), mobile fulcrum and eccentric wheel (21), mobile fulcrum moves along lever arm, its travel direction is the axial direction due of lever arm, and wherein eccentric minimum radius is equal to the distance of lever arm with its axle center.
11. systems according to claim 10, wherein move fulcrum and comprise traversing carriage (23), traversing carriage driving mechanism (24) and mobile fulcrum shaft (37), lever arm has the hollow groove parallel with its upper surface, mobile fulcrum shaft is through hollow groove, move in hollow groove under traversing carriage driving mechanism drives, form the mobile fulcrum of lever.
12. systems according to claim 1, wherein said needle is permanent magnet material.
13. systems according to claim 1, wherein said sleeve pipe is nonmagnetic substance.
14. systems according to claim 1, wherein biologically active substance is cell, protein or nucleic acid.
15. systems according to claim 1, wherein said biologically active substance extraction apparatus is the instrument for Isolation and purification nucleic acid.
16. 1 kinds, for extracting the instrument of biologically active substance, comprising:
Shell and base plate (1),
Worktable (15), it has sample preparation district,
Needle according to any one of claim 1-15 and sleeve pipe mobile system.
17. 1 kinds of methods using the instrument Isolation and purification biologically active substance described in claim 16.
CN201310014647.5A 2013-01-15 2013-01-15 The needle of bar magnet method extraction apparatus and sleeve pipe mobile system are applied with it Expired - Fee Related CN103923829B (en)

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